No functional TRPA1 in cardiomyocytes

• Published in: Acta Physiologica 2021-08, Vol.232 (4), p.e13659-n/a
• Main Authors: Hoebart, Clara, Rojas‐Galvan, Natalia S., Ciotu, Cosmin I., Aykac, Ibrahim, Reissig, Lukas F., Weninger, Wolfgang J., Kiss, Attila, Podesser, Bruno K., Fischer, Michael J. M., Heber, Stefan
• Format: Article
• Language: English
• Subjects: Acetamides; Agonists; Animals; Calcium conductance; Capsaicin; Capsaicin receptors; Cardiomyocytes; Cardiovascular Physiology; Cell differentiation; Cell lines; Dorsal root ganglia; Ganglia, Spinal; Heart; human; Humans; Mice; mouse; mRNA; Myocytes, Cardiac; Pluripotency; Regular Paper; Stem cell transplantation; Stem cells; Thiazoles; Transient Receptor Potential Channels; TRPA1; TRPA1 Cation Channel; TRPV Cation Channels; TRPV1
• ISSN: 1748-1708; 1748-1716; 1748-1716
• DOI: 10.1111/apha.13659

Aim There is mounting evidence that TRPA1 has a role in cardiac physiology and pathophysiology. We aim to clarify the site of TRPA1 expression in the heart and in particular whether the channel is expressed in cardiomyocytes. Methods Due to the high calcium conductance of TRPA1, and marginal calcium changes being detectable, microfluorimetry in primary mouse cardiomyocytes, and in the cardiomyocyte cell lines H9c2 and HL‐1, was applied. TRPA1 mRNA in mouse and human hearts, primary cardiomyocytes, and the cardiac cell lines were quantified. Dorsal root ganglia served as control for both methods. Results In addition to AITC, the more potent and specific TRPA1 agonists JT010 and PF‐4840154 failed to elicit a TRPA1‐mediated response in native and electrically paced primary cardiomyocytes, and the cardiomyocyte cell lines H9c2 and HL‐1. There were only marginal levels of TRPA1 mRNA in cardiomyocytes and cardiac cell lines, also in conditions of cell differentiation or inflammation, which might occur in pathophysiological conditions. Similarly, TRPV1 agonist capsaicin did not activate primary mouse cardiomyocytes, did not alter electrically paced activity in these, and did not activate H9c2 cells or alter spontaneous activity of HL‐1 cells. Human pluripotent stem cells differentiated to cardiomyocytes had no relevant TRPA1 mRNA levels. Also in human post‐mortem heart samples, TRPA1 mRNA levels were substantially lower compared with the respective dorsal root ganglion. Conclusion The results do not question a role of TRPA1 in the heart but exclude a direct effect in cardiomyocytes.